Pharmacokinetic and clinical studies on teicoplanin for sepsis by methicillin-cephem resistant Staphylococcus aureus in the pediatric and neonate field

Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrated dose for pediatrics patients was 10 mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals. 1. Pharmacokinetic results. All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60 micrograms/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8 micrograms/mL, and in pediatrics were 12.5, 12.2 and 13.1 micrograms/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients. 2. Efficacy and safety results. Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood. Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs. Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, gamma-GTP increased, GOT increased and GPT increased in 3 pediatrics. These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.     

The clinical significance of follow-up sonography in the detection of cervical lymph node metastases in patients with stage I or II squamous cell carcinoma of the tongue

OBJECTIVE: We sought to assess the reliability of repeated sonography in the detection of cervical lymph node metastases at the earliest stage during a follow-up period in patients with stage I or stage II carcinoma of the tongue. STUDY DESIGN: Eighteen consecutive patients with stage I or II squamous cell carcinoma of the tongue were included. When possible, every patient was examined with sonography approximately every 2 weeks during the follow-up period. RESULTS: With repeated sonography on 18 patients, 7 metastatic nodes of 7 patients (39%) meeting our criteria were found. With the use of computed tomography, we diagnosed 10 nodes (including the 7 nodes observed with sonography) in these 7 patients as metastatic. A histopathologic examination revealed that 12 nodes in the same 7 patients had metastatic foci. For sonography, the sensitivity per node was 58%, whereas that of computed tomography was 83%. CONCLUSIONS: Follow-up sonography enabled the detection of all patients who had subsequent subclinical lymph node metastases. However, the sensitivity of sonography in the detection of smaller metastatic nodes was lower than that of computed tomography.     

Impact of Prol2Ala variant in the peroxisome proliferator-activated receptor (PPAR) gamma2 on obesity and insulin resistance in Japanese Type 2 diabetic and healthy subjects

The peroxisome proliferator-activated receptor (PPAR) gamma is an important regulator of adipocyte differentiation and a modulator of intracellular insulin-signaling events. We examined the roles of the Pro12Ala variant of PPAR gamma2 in obesity and insulin resistance in 402 Japanese patients with type 2 diabetes and 116 control subjects. Among the diabetes subjects, the Pro12Pro homozygotes showed significantly higher body mass index (BMI) than those with the Pro12Ala variant (p = 0.020), while there was no association between genotype and BMI in the controls. Furthermore, diabetic subjects with Pro12Pro showed significantly higher fat body mass index (FBMI) than those with Pro12Ala (p = 0.016), while no association between genotype and lean body mass index (LBMI) was observed. Regarding insulin resistance, there was no difference in the HOMA index or in clamp index between Pro12Ala and Pro12Pro variants. These data suggest that the Pro12Ala polymorphism of PPAR gamma2 does not influence insulin resistance but body composition in Japanese diabetic subjects.     

A case report of both CAF and docetaxel-resistant breast cancer responding to paclitaxel weekly therapy

A 58-year-old woman underwent CAF and docetaxel therapy for lung, liver and bone metastases from breast cancer operated on 14 years ago. Because of progressive disease due to secondary resistance to CAF and docetaxel, the patient was given three courses of paclitaxel therapy (60 mg/m2, day 1, 8, 15, repeated every 4 weeks). The paclitaxel weekly therapy brought about no adverse effects and remarkable effects against lung and liver metastases (PR). Although the duration of the response to the paclitaxel therapy was limited to about two months due to the progression of skull bone metastasis, paclitaxel weekly therapy may be effective against both CAF and docetaxel-resistant breast cancer.     

Mental state as a possible independent prognostic variable for survival in patients with advanced lung carcinoma

BACKGROUND: Although psychologic factors have been reported to influence the progression of cancer, this theory remains controversial. A prospective study of patients with advanced lung carcinoma was performed to explore the influence of the patient's mental state on survival. METHODS: The patient's mental state was assessed with the Tokyo University Egogram. In a preliminary study, the egograms of long-term survivors (survival > 3 years) with TNM Stage IIIB or Stage IV lung carcinoma were compared with the egograms of consecutive, newly diagnosed lung carcinoma patients (controls). Next, in a prospective study, 123 patients with nonsmall cell lung carcinoma and 56 patients with small cell lung carcinoma (Stage IIIB or Stage IV; Eastern Cooperative Oncology Group performance status of 0 or 1) completed the egogram. Based on the results of the preliminary study, the subjects in the prospective study were divided into Group A (Free Child [FC] >or= 50th percentile and Adapted Child [AC] < 50th percentile) and Group B (FC < 50 percentile or AC >or= 50 percentile). The survival of the two groups was compared. The Cox proportional hazards model was used to determine the joint effect of the patient's mental state and other prognostic factors. RESULTS: In the preliminary study, the FC score of the long-term survivors was significantly higher and the AC score was significantly lower than those of the controls. In the prospective study, the survival of Group A was significantly longer than that of Group B both in the nonsmall cell lung carcinoma and small cell lung carcinoma patients (P = 0.002 and P = 0.005, respectively, by the log-rank test). Multivariate analysis demonstrated that after adjustment for clinical factors, being in Group A was a significant predictor of survival both in the nonsmall cell and small cell lung carcinoma patients. CONCLUSIONS: The results of the current study demonstrate that the mental state of the patient as assessed by the egogram may have prognostic significance in patients with advanced lung carcinoma.     

Computer detection of cognitive impairment and associated neuropsychiatric dimensions from the content analysis of verbal samples

This is a report of a study testing the capacity of a computerized measure of the content analysis of five minute verbal samples to detect and measure cognitive impairment and comorbid neuropsychiatric dimensions in 117 drug-abusing inpatients. The cognitive impairment scores obtained from the computerized procedure correlated significantly with independent scores from the Trails B and Stroop Color and Word test as well as with ANAM (Automated Neuropsychiatric Assessment Metric) neuropsychological tests, including the Matching to Sample Efficiency and Accuracy, the Code Substitution Efficiency, the Continuous Performance Task Efficiency and Accuracy, the Code Substitution Delayed Recall Accuracy, and the Simple Reaction Time Efficiency. When the computerized verbal-content-analysis-derived cognitive impairment scores were combined with scores of selected other ANAM measures, more and higher intercorrelations occurred with Trails A, Trails B, the Stroop Color and Word test, and the Wisconsin Card Sort test. In addition, validated measures of a broad range of associated neuropsychiatric dimensions can be obtained simultaneously from the same five minute verbal samples providing the cognitive impairment scores. No significant effects were found on the cognitive impairment scores of age, education, gender, race, and duration of drug-abuse abstinence.     

The prognostic significance of overexpression of the decoy receptor for Fas ligand (DcR3) in patients with gastric carcinomas

Abstract. Background: The FasL-Fas system has an important role in mediating immune-cytotoxic killing of cells such as virus-infected or tumor cells. It was recently reported that there is a soluble decoy receptor (DcR3), which binds to FasL and inhibits FasL-induced apoptosis, and certain tumors may escape FasL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FasL. We evaluated whether DcR3 has clinical relevance in actual human gastric cancers. Methods: . The expression of DcR3 was investigated by Northern blot analysis in a series of 84 primary gastric carcinomas and compared with clinicopathological features and prognosis. The DcR3 expression level was analyzed and quantified densitometrically. The location of DcR3 mRNA in gastric carcinoma tissue was detected by in situ hybridization. Results: The frequency of DcR3 overexpression was 26% (22 of 84 surgical specimens). The DcR3 expression level was significantly associated with lymph node metastasis and pathological stage, but did not correlate with tumor size, metastatic status, or histological type. In situ hybridization demonstrated that DcR3 mRNA was expressed in tumor cells. When the patients were followed up for 63 months, DcR3 overexpression was found to be associated with a significantly shortened duration of overall survival compared with findings in patients having normal DcR3 expression. Conclusion: The DcR3 decoy receptor for FasL may be involved in the progression of gastric cancer. Further evaluation of these possible roles of DcR3 and the regulation of DcR3 expression in malignant cells will be critically important for the development of new strategies for controlling the growth of malignant cells that escape host immune surveillance. Received: July 19, 2001 / Accepted: December 21, 2001